Neuropediatrics 2011; 42(06): 227-233
DOI: 10.1055/s-0031-1295493
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

COL4A1 Mutations Associated with a Characteristic Pattern of Intracranial Calcification

J. Livingston
1  Department of Paediatric Neurology, Leeds General Infirmary, Leeds, UK
,
D. Doherty
2  Divisions of Developmental Medicine and Genetic Medicine, University of Washington Seattle Childrens Hospital, Seattle, Washington, USA
,
S. Orcesi
3  Unit of Child Neurology and Psychiatry, IRCCS “C. Mondino Institute of Neurology” Foundation, Pavia, Italy
,
D. Tonduti
3  Unit of Child Neurology and Psychiatry, IRCCS “C. Mondino Institute of Neurology” Foundation, Pavia, Italy
,
A. Piechiecchio
3  Unit of Child Neurology and Psychiatry, IRCCS “C. Mondino Institute of Neurology” Foundation, Pavia, Italy
,
R. La Piana
4  Department of Neuroradiology, Montreal Neurological Institute, Montreal, CanadaM
,
E. Tournier-Lasserve
5  Laboratoire de Genetique, Groupe Hospatilier Lariboisiere-­Fernand-Widal, Paris, France
,
A. Majumdar
6  Department of Paediatric Neurology, Bristol Children’s Hospital, Bristol, UK
,
S. Tomkins
7  Department of Clinical Genetics, Bristol, UK
,
G. Rice
8  Department of Genetic Medicine, Manchester Academic Health Science Centre, Central Manchester Foundation Trust University Hospitals, University of Manchester, Manchester, UK
,
R. Kneen
9  Neuroscience Unit, Alder Hey Childrens NHS Foundation Trust, Littlewood, Liverpool, UK
,
M. van der Knaap
10  Department of Child Neurology VU University Medical Center, Amsterdam, The Netherlands
,
Y. Crow
11  Department of Genetic Medicine, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK
› Author Affiliations
Further Information

Publication History

received 01 October 2011

accepted 09 November 2011

Publication Date:
01 December 2011 (eFirst)

Abstract

Introduction:

Intracranial calcification (ICC) is a relatively common radiological finding in children undergoing investigation for neurological disorders. Many causes are recognised, and ICC is often regarded as a non-specific sign.

Methods:

From an ongoing study of ICC, we identified 5 patients with characteristic radiological features, in whom a mutation in the COL4A1 gene was found.

Results:

All patients had CT and MR imaging. MR images demonstrated features of periventricular leukomalacia with irregular dilatation of the lateral ventricles with or without porencephaly, loss of hemispheric white matter volume, and high signal on T2 and FLAIR sequences within periventricular and deep white matter. Calcification was apparent on MR in 4 patients. CT scans demonstrated spot and linear calcification in the subependymal region and around areas of porencephaly. Calcification was also visible in the deep cerebral white matter and basal ganglia. 1 patient showed calcification in the central pons.

Conclusion:

ICC occurs in COL4A1-related disease. The radiological features are distinct from other conditions demonstrating recognisable patterns of ICC, such as congenital cytomegalovirus infection and Aicardi-Goutiéres syndrome. In the absence of a known risk factor for periventricular leukomalacia, the presence of these radio­logical findings should suggest the possibility of COL4A1-related disease.